Although heparin is a widely used anticoagulant, our knowledge of its clinical pharmacology is far from complete. Its clinical use continues to be associated with relatively high incidence of hemorrhagic complications and insufficient therapy. It is proposed to compare "chemical" titration and biological assays and to apply these to further elucidate the effects of dose, duration of therapy and plasma binding on the pharmacokinetics and efficacy of heparin. The biological effects to be measured include its anticoagulant, anti-platelet, and free fatty acid releasing properties. Several plasma proteins (albumin, globulins, fibrinogen, antithrombin III) and in vitro tests (relationship between biologic effect and heparin added to plasma) that may be determinants of its pharmacokinetics and pharmacodynamics will also be monitored. In addition, the pharmacokinetic effects of reduced plasma binding of propranolol produced by free fatty acid release will be investigated. The effects of free fatty acid release on plasma binding of several other drugs will also be investigated. These studies should enhance our ability to individualize therapy with heparin and increase our knowledge of the effects of binding displacement drug interactions.